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Methotrexate-loaded biodegradable nanoparticles exert anti-arthritic effect by downregulating pro-inflammatory cytokines in Freund’s complete adjuvant-induced arthritic rats

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Abstract

Methotrexate (MTX), the first-line drug for the treatment of rheumatoid arthritis (RA), can cause considerable toxicity, which limits effective dosage regimens. Moreover, it has rapid clearance, which leads to poor patient compliance. To mitigate such challenges, this study aimed to validate the use of MTX-loaded chitosan nanoparticles (NPs) in treating Freund’s complete adjuvant (FCA) arthritis in rats. Healthy Wistar rats (n = 30) were divided into five groups. The first group served as healthy control, while the second group served as arthritic control. Group 3 was administered methotrexate, while groups 4 and 5 were MTX-loaded NP-treated groups. NPs were prepared by solvent evaporation method and characterized by zeta size, potential, polydispersity index (PDI), and Fourier-transform infrared spectroscopy. NPs were 190 nm in size, and PDI was 0.25, confirming the uniform distribution of NPs. A significant increase in paw thickness was noted up to the 21st day of the study, which was reversed by a high dose of MTX-loaded NPs. MTX NPs significantly reduced the level of pro-inflammatory markers, including TNF-α and IL-6, along with improving control of oxidative stress biomarkers. The findings of biochemical, haematological, radiological, and histopathological investigations further confirmed amelioration of necrosis and cellular infiltration. It can be concluded that MTX-loaded chitosan NPs are promising candidates for treating FCA-induced arthritis in a rat model.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The study has not received any funding.

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Authors and Affiliations

  1. Institute of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan

    Muhammad Usman Saleem & Faqir Muhammad

  2. Department of Pharmacy, University of Agriculture, Faisalabad, Pakistan

    Bushra Akhtar

  3. Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Lahore, Pakistan

    Ali Sharif

  4. Institute of Microbiology, University of Agriculture, Faisalabad, Pakistan

    Muhammad Imran Arshad

  5. Department of Physics, University of Agriculture, Faisalabad, Pakistan

    Kanwal Akhtar & Yasir Javed

Authors
  1. Muhammad Usman Saleem
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  2. Faqir Muhammad
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  3. Ali Sharif
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  4. Muhammad Imran Arshad
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  5. Kanwal Akhtar
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  6. Yasir Javed
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  7. Bushra Akhtar
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by MUS, BA, AS, FM, MIA, KA, and YJ. The first draft of the manuscript was written by MUS and BA, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Bushra Akhtar.

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All the in vivo experiments were conducted after approval from the institutional ethics committee.

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Saleem, M.U., Muhammad, F., Sharif, A. et al. Methotrexate-loaded biodegradable nanoparticles exert anti-arthritic effect by downregulating pro-inflammatory cytokines in Freund’s complete adjuvant-induced arthritic rats. Inflammopharmacol 30, 1079–1091 (2022). https://doi.org/10.1007/s10787-022-00977-1

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  • DOI: https://doi.org/10.1007/s10787-022-00977-1

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